The hygiene hypothesis goes on trial…

If there is one thing that excites me about the biotech industry, it’s the possibility that everything that we think we know about how to treat a disease will get turned on its head. A great example of this is the Nobel Prize winning work by Barry Marshall and Robin Warren on the role of H. pylori and stomach ulcers. Despite the dogma at the time that blamed ulcers on stress and poor diet, Marshall and Warren combined creative thinking and careful scientific exploration to prove all of it wrong. And to top it all off, their discovery lead to a treatment regime that cures H. pylori infections (and typically ulcers as well) in over 80% of patients.

T. suis ova

Coronado Biosciences isn’t there yet, but they just announced that they will be submitting an IND application later this year for their novel treatment of Crohn’s disease, CNDO-201. What makes this treatment so unique is that it composed of T. suis ova, or, as they are more commonly called, pig whipworm eggs. The theory behind this treatment is the so-called “hygiene hypothesis“, or the idea that as we improve our living conditions through the elimination of what were once common infections, we are disrupting the development of our immune system. Since humans have suffered from these infections for hundreds of thousands of years, the thought is that our immune system depends on exposure to these pathogens for its proper development. Immune system regulation pathways are far from simple, so I’ll leave it up to the reader to investigate the details, but simply put, the hypothesis is based on T-helper cell feedback between Th1 and Th2 cells. Basically, stimulating Th1 cells (through exposure to bacteria and virus) downregulates Th2 activity, which is responsible for the inappropriate immune responses that lead to conditions such as allergies and eczema. It gets even more complicated when we start talking about autoimmune diseases such as Crohn’s disease or multiple sclerosis, since these are Th1 mediated immune responses, however, theories have been put forth to explain the role of pathogen exposure in these diseases as well.

What makes this news so exciting is that Coronado Biosciences is prepared to move forward with clinical trials in this area based on some very positive data from a number of independent investigator trials (you can find the trial results on their website). In one open-label, non-comparative study of 29 patients with Crohn’s disease, 66% of patients entered remission at 12 weeks and this increased to 72% of patients at 24 weeks. This is quite remarkable as the tool-of-last-resort for treating Crohn’s disease, anti-TNF-alpha drugs such as Remicade and Humira typically see remission rates in ~30% of patients. The caveat of course is that this was a open-label study with a small number of patients and until more rigorous studies are completed, we won’t truly know the efficacy of this treatment. Until then, I’ll keep my fingers crossed and continue to give Coronado Biosciences a pat on the back for exploring a truly novel treatment paradigm, that if successful, could fundamentally change how we treatment autoimmune diseases.